scholarly journals Environmental Factors, Lifestyle Risk Factors, and Host Characteristics Associated With Philadelphia Negative Myeloproliferative Neoplasm: A Systematic Review

2021 ◽  
Vol 28 ◽  
pp. 107327482110468
Author(s):  
Niloofar Allahverdi ◽  
Mohamed Yassin ◽  
Mohamed Ibrahim
Keyword(s):  
Risk Factors ◽  
Environmental Factors ◽  
Myeloproliferative Neoplasms ◽  
Grey Literature ◽  
Myeloproliferative Neoplasm ◽  
Hazardous Substances ◽  
Hematopoietic Stem ◽  
Proinflammatory Mediators ◽  
Increased Risk ◽  
Host Characteristics

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated with an acquired genetic mutation of Janus Kinase2V617F. Various epidemiological studies have indicated associations between environmental factors, lifestyle factors, and host characteristics with developing MPNs. This review aims to collect and summarize the existing information on these risk factors and establish their association with pathogenesis MPNs. Medline, Embase, PubMed, and grey literature were systematically searched using key terms for MPNs, and epidemiological study designs, that is, cross-sectional studies, case-control, and cohort, that investigated the risk factors for MPNs published were identified. Out of the 4621 articles identified, 20 met the selection criteria and were included in this review. Heterogeneity, study reliability, and bias were assessed. A significant association was found between smoking and the development of MPNs. This relationship has been explained by the substantial increase in several proinflammatory mediators and systematic oxidative stress causing hyperstimulation of myeloid compartments leading to the development of MPNs. Obesity was modestly linked with an increased risk of MPNs. The underlying mechanisms have been linked to changes in endocrine, metabolic, and inflammatory systems. No strong association was found between exposure to hazardous substances, that is, benzene and MPNs, but further investigation on the effects of increased levels and duration of exposure on hematopoietic stem cells will be beneficial. Unique individual and host variations have been determined as a modifier of disease pathogenesis and phenotype variations. There is a higher incidence rate of females developing MPNs, specifically ET, than males with higher PV incidence. Therefore, gender contributes to the heterogeneity in myeloproliferative neoplasm. Studies identified as part of this review are very diverse. Thus, further in-depth assessment to explore the role of these etiological factors associated with MPNs is warranted.

scholarly journals Cell competition between wild-type and JAK2V617F mutant cells in a murine model of a myeloproliferative neoplasm

2020 ◽  
Author(s):  
Melissa Castiglione ◽  
Haotian Zhang ◽  
Huichun Zhan
Keyword(s):  
Stem Cell ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
List Type ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mutant Cells

AbstractThe myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by overproduction of mature blood cells and increased risk of transformation to frank leukemia. The acquired kinase mutation JAK2V617F plays a central role in a majority of these disorders. The hematopoietic stem cell (HSC) compartment in MPN is heterogeneous with the presence of both JAK2 wild-type and JAK2V617F mutant cells in most patients with MPN. Utilizing in vitro co-culture assays and in vivo competitive transplantation assays, we found that the presence of wild-type cells altered the behavior of co-existing JAK2V617F mutant cells, and a mutant microenvironment (niche) could overcome the competition between wild-type and mutant cells, leading to mutant clonal expansion and overt MPN. We also demonstrated that competition between wild-type and JAK2V617F mutant cells triggered a significant immune response, and there was a dynamic PD-L1 deregulation in the mutant stem/progenitor cells caused by their interactions with the neighboring wild-type cells and the microenvironment. Therefore, while accumulation of oncogenic mutations is unavoidable during aging, our data suggest that, if we could therapeutically enhance normal cells’ ability to compete, we might be better able to control neoplastic cell expansion and prevent the development of a full-blown malignancy.Key PointsThe presence of wild-type cells alters the behavior of co-existing JAK2V617F mutant cellsA mutant microenvironment overcomes the competition between wild-type and JAK2V617F mutant cells, leading to the development of a MPN

Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4358-4366 ◽  
Author(s):  
Kieren A. Marr ◽  
Rachel A. Carter ◽  
Michael Boeckh ◽  
Paul Martin ◽  
Lawrence Corey
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Invasive Aspergillosis ◽  
Respiratory Virus ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Cmv Disease

The incidence of postengraftment invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients increased during the 1990s. We determined risks for IA and outcomes among 1682 patients who received HSCTs between January 1993 and December 1998. Risk factors included host variables (age, underlying disease), transplant variables (stem cell source), and late complications (acute and chronic graft-versus-host disease [GVHD], receipt of corticosteroids, secondary neutropenia, cytomegalovirus [CMV] disease, and respiratory virus infection). We identified risk factors associated with IA early after transplantation (≤ 40 days) and after engraftment (41-180 days). Older patient age was associated with an increased risk during both periods. Chronic myelogenous leukemia (CML) in chronic phase was associated with low risk for early IA compared with other hematologic malignancies, aplastic anemia, and myelodysplastic syndrome. Multiple myeloma was associated with an increased risk for postengraftment IA. Use of human leukocyte antigen (HLA)–matched related (MR) peripheral blood stem cells conferred protection against early IA compared with use of MR bone marrow, but use of cord blood increased the risk of IA early after transplantation. Factors that increased risks for IA after engraftment included receipt of T cell–depleted or CD34-selected stem cell products, receipt of corticosteroids, neutropenia, lymphopenia, GVHD, CMV disease, and respiratory virus infections. Very late IA (> 6 months after transplantation) was associated with chronic GVHD and CMV disease. These results emphasize the postengraftment timing of IA; risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.

scholarly journals A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Paola Villafuerte-Gutiérrez ◽  
Montserrat López Rubio ◽  
Pilar Herrera ◽  
Eva Arranz
Keyword(s):  
Kinase Inhibitors ◽  
Fusion Gene ◽  
Myeloproliferative Neoplasms ◽  
Therapeutic Option ◽  
Myeloproliferative Neoplasm ◽  
Allogeneic Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Health Organization

Hematopoietic myeloproliferative neoplasms with FGFR1 rearrangement result in the 8p11 myeloproliferative syndrome that in the current Word Health Organization classification is designated as “myeloid and lymphoid neoplasm with FGFR1 abnormalities.” We report the case of a 66-year-old man who had clinical features that resembled chronic myeloid leukaemia (CML), but bone marrow cytogenetic and fluorescent in situ hybridization (FISH) studies showed t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. He was initially managed with hydroxyurea, and given the aggressive nature of this disease, four months later, the patient underwent an allogeneic hematopoietic stem-cell transplantation (HSCT) from an HLA-haploidentical relative. Currently, HSCT may be the only therapeutic option for long-term survival at least until more efficacious tyrosine kinase inhibitors (TKIs) become available.

scholarly journals The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2316
Author(s):  
Lucia Catani ◽  
Michele Cavo ◽  
Francesca Palandri
Keyword(s):  
Extracellular Vesicles ◽  
Immune Escape ◽  
Myeloproliferative Neoplasms ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Driver Genes ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Patients Experience

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

scholarly journals Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR–ABL-Negative Myeloproliferative Neoplasm

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1037
Author(s):  
Alessandro Allegra ◽  
Giovanni Pioggia ◽  
Alessandro Tonacci ◽  
Marco Casciaro ◽  
Caterina Musolino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Chronic Inflammation ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Tumor Stage ◽  
Driver Mutations ◽  
Hematopoietic Stem ◽  
Chronic Myeloproliferative Neoplasms ◽  
Inflammatory State

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In BCR–ABL1-negative MPNs, the driver mutations include JAK 2, MPL, and CALR. Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.

scholarly journals Impact of Host, Lifestyle and Environmental Factors in the Pathogenesis of MPN

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2038
Author(s):  
Gajalakshmi Ramanathan ◽  
Brianna M Hoover ◽  
Angela G Fleischman
Keyword(s):  
Environmental Factors ◽  
Myeloproliferative Neoplasms ◽  
Driver Mutation ◽  
Lifestyle Modifications ◽  
Hematopoietic Stem ◽  
Inflammatory Stimuli ◽  
Progression Of Disease ◽  
Development Support ◽  
Traditional Risk Factors ◽  
Hallmark Feature

Philadelphia-negative myeloproliferative neoplasms (MPNs) occur when there is over-production of myeloid cells stemming from hematopoietic stem cells with constitutive activation of JAK/STAT signaling, with JAK2V617F being the most commonly occurring somatic driver mutation. Chronic inflammation is a hallmark feature of MPNs and it is now evident that inflammation is not only a symptom of MPN but can also provoke development and precipitate progression of disease. Herein we have considered major MPN driver mutation independent host, lifestyle, and environmental factors in the pathogenesis of MPN based upon epidemiological and experimental data. In addition to the traditional risk factors such as advanced age, there is evidence to indicate that inflammatory stimuli such as smoking can promote and drive MPN clone emergence and expansion. Diet induced inflammation could also play a role in MPN clonal expansion. Recognition of factors associated with MPN development support lifestyle modifications as an emerging therapeutic tool to restrain inflammation and diminish MPN progression.

scholarly journals Outcome of Pregnancy in the Era of Pegylated Interferon Alpha 2a in Females with Essential Thrombocythemia: An Experience from Qatar

2020 ◽  
Vol 13 (1) ◽  
pp. 336-340
Author(s):  
Mohammad Abu-Tineh ◽  
Nancy Kassem ◽  
Mohammad Abdul-Jaber Abdulla ◽  
Omar Mohammad Ismail ◽  
Rola Ghasoub ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Pegylated Interferon ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Pegylated Interferon Alpha ◽  
Pregnant Females ◽  
Increased Risk ◽  
Hemorrhagic Complications

Myeloproliferative neoplasms are a diversified group of diseases of the hematopoietic stem cell, such as essential thrombocythemia (ET) and polycythemia vera. They are mainly caused by mutations in the following genes: JAK2, CALR, and MPL. All carry an increased risk to transform into acute leukemia or chronic myelogenous leukemia along with thrombosis and hemorrhagic complications. Treatment of such disorders during pregnancy is a challenging footstep, given the high risk of complications for both the mother and the fetus. Here, we report about two pregnant females with ET that has been treated with pegylated interferon alpha with safe and effective outcome.

scholarly journals Body Mass Index and Total Symptom Burden in Myeloproliferative Neoplasms Discovery of a U-shaped Association

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2202 ◽  
Author(s):  
Sarah Friis Christensen ◽  
Robyn Marie Scherber ◽  
Nana Brochmann ◽  
Martin Goros ◽  
Jonathan Gelfond ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Symptom Burden ◽  
Normal Weight ◽  
Analysis Of Covariance ◽  
Cross Sectional ◽  
Increased Risk

Elevated body mass index (BMI) is a global health problem, leading to enhanced mortality and the increased risk of several cancers including essential thrombocythemia (ET), a subtype of the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). Furthermore, evidence states that BMI is associated with the severity of symptom burden among cancer patients. MPN patients often suffer from severe symptom burden. The purpose of this study was to examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced quality of life (QoL). A combined analysis of two large cross-sectional surveys, the Danish Population-based Study, MPNhealthSurvey (n = 2044), and the international Fatigue Study (n = 1070), was performed. Symptoms and QoL were assessed using the validated Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, sex, and MPN subtype. A U-shaped association between BMI and Total Symptom Burden was observed in both datasets with significantly higher mean scores for underweight and obese patients relative to normal weight (mean difference: underweight 5.51 (25.8%), p = 0.006; obese 5.70 (26.6%) p < 0.001). This is an important finding, as BMI is a potentially modifiable factor in the care of MPN patients.

scholarly journals JAK2 V617F impairs hematopoietic stem cell function in a conditional knock-in mouse model of JAK2 V617F–positive essential thrombocythemia

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1528-1538 ◽  
Author(s):  
Juan Li ◽  
Dominik Spensberger ◽  
Jong Sook Ahn ◽  
Shubha Anand ◽  
Philip A. Beer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Essential Thrombocythemia ◽  
Cell Function ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Transgenic Models ◽  
Disease Phenotype ◽  
Hematopoietic Stem

The JAK2 V617F mutation is found in most patients with a myeloproliferative neoplasm and is sufficient to produce a myeloproliferative phenotype in murine retroviral transplantation or transgenic models. However, several lines of evidence suggest that disease phenotype is influenced by the level of mutant JAK2 signaling, and we have therefore generated a conditional knock-in mouse in which a human JAK2 V617F is expressed under the control of the mouse Jak2 locus. Human and murine Jak2 transcripts are expressed at similar levels, and mice develop modest increases in hemoglobin and platelet levels reminiscent of human JAK2 V617F–positive essential thrombocythemia. The phenotype is transplantable and accompanied by increased terminal erythroid and megakaryocyte differentiation together with increased numbers of clonogenic progenitors, including erythropoietin-independent erythroid colonies. Unexpectedly, JAK2V617F mice develop reduced numbers of lineage−Sca-1+c-Kit+ cells, which exhibit increased DNA damage, reduced apoptosis, and reduced cell cycling. Moreover, competitive bone marrow transplantation studies demonstrated impaired hematopoietic stem cell function in JAK2V617F mice. These results suggest that the chronicity of human myeloproliferative neoplasms may reflect a balance between impaired hematopoietic stem cell function and the accumulation of additional mutations.

Risk of Thromboembolic Events in ET and Early/Prefibrotic PMF: The Relevance of an Accurate Histological Diagnosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1735-1735
Author(s):  
Serena Rupoli ◽  
Gaia Goteri ◽  
Picardi Picardi ◽  
Lucia Canafoglia ◽  
Giorgia Micucci ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasm ◽  
Primary Myelofibrosis ◽  
Vascular Events ◽  
Bone Marrow Trephine Biopsy ◽  
Increased Risk ◽  
Risk Patients ◽  
Early Primary

Abstract Abstract 1735 Background: Essential Thrombocytemia (ET) is a myeloproliferative neoplasm characterized by increased risk of vascular events. Established thrombosis risk factors are age and previous vascular events. The clinical and prognostic relevance of WHO histologic criteria for ET and prefibrotic/early Primary Myelofibrosis (PMF) has been well recognized. Our aim was to evaluate the correlation between histologic interpretation and vascular events in our series of thrombocytemias. Material and methods: From our files, we retrieved all patients consecutively diagnosed as having ET with complete clinical data (N = 283) who had undergone to a bone marrow trephine biopsy before any treatment at or within 1 year of diagnosis (N= 133). The histologic slides were reviewed in order to separate true ET cases from early/prefibrotic PMF; vaso-occlusive events at diagnosis and in the follow-up were than compared in the two groups. Results: Histologic review reclassified 61 cases as ET and 72 cases as prefibrotic/early PMF. Prefibrotic/early PMF showed a significant higher prevalence of thrombosis history and thrombotic events at diagnosis, and an increased leukocyte count than ET (22% vs 8%, 15.2% vs 1.6%, 8389/mmc vs 7500/mmc, respectively); furthermore, venous thromboses (mainly atypical) were relatively common in PMF, as opposed to WHO-defined ET. During follow-up, patients with prefibrotic PMF, although younger, showed a significant higher risk of developing thrombosis: the 15-year risk of thrombosis was 48% in prefibrotic PMF (grade 0), 16% in early PMF (grade 1, 2) and 17% in ET. Multivariate analysis confirmed that age and histopathology are independent risk factors for thrombosis during follow-up. Patients older than 60 or with prefibrotic PMF are high risk patients whereas those younger and with non prefibrotic PMF or ET should be considered at low risk (20-year risk of thrombosis 47% vs 4%, p=0.005). Conclusion: The results of present study indicate prefibrotic PMF as a myloproliferative neoplasm with the highest tendency to develop vascular events compared to early PMF and ET. Therefore we suggest to include histopathology interpretation in the risk stratification of so-called ET patients. Disclosures: No relevant conflicts of interest to declare.

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